Optimizing intranasal distribution and retention of topical therapy is essential in the management of patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). Computational fluid dynamics analysis has not previously been used to investigate sinus nasal spray delivery in the complete post-operative sinonasal geometries of patients who have undergone FESS. Models of sinonasal cavities were created from postoperative magnetic resonance imaging scans in four patients, three of whom underwent a comprehensive FESS, the other a modified endoscopic Lothrop procedure. Spray simulations were conducted at different flow rates (5 L/min, 10 L/min and 15 L/min) using sixteen particle sizes ranging from 4 μm to 70μm, spray velocity of 10 m/s and plume angle of 15°. Two different spray insertion angles were compared. Airflow distribution in the sinuses was closely related to the patient's nasal geometry and surgical intervention, in particular a unique crossflow between nasal chambers was present for the Lothrop patient. Sinus deposition was generally more effective with inhalational transport of low-inertia particles outside of the range produced by many standard nasal sprays or nebulizer. This was true except in the Lothrop patient, since previous surgery had been performed removing most of the septum where high-inertia particles would normally deposit. For sinuses receiving minimal airflow, particle penetration was diminished and successful deposition in the region became more restricted by device parameters. Further research is needed to validate these findings and explore other spray variables in a wider spectrum of patients to ascertain a multi-level approach to optimizing drug delivery in the sinuses.